Significance of G-protein-coupled-receptor activating the JAK-STAT pathway.. Cardiac hypertrophy has been attributed to myocyte re-expresslon of fetal embryonic genes. Cardiac hypertrophy of myocytes has been shown to precede myocyte heart failure. The hypothesis of this proposal is that the angiotensin II receptor (type I) signals through the JAK-STAT signaling pathway to activate gene expression in myocyte hypertrophy. The loss of STAT3 in the cardiac cell survival pathway has been shown to be a critical event in the onset of heart failure during mechanical stress. Recent reports suggest that JAK-STAT signaling is cardio-protective against ischemia in the heart. In this grant proposal, we plan to elucidate the function of JAK-STAT signaling in the heart by defining the gene targets for this signaling pathway, and identifying the functional elements in the GPCR angiotensin II type I receptor that are responsible for the coupling to the cytokine signaling pathway.